The following medications have been administered with ZENAPAX in clinical trials in renal allograft patients with no incremental increase in adverse reactions: cyclosporine, mycophenolate mofetil, ganciclovir, acyclovir, azathioprine, and corticosteroids. Very limited experience exists in these patients with the use of ZENAPAX concomitantly with tacrolimus, muromonab-CD3, antithymocyte globulin, and anti-lymphocyte globulin.
In renal allograft recipients (n=50) treated with ZENAPAX and mycophenolate mofetil, no pharmacokinetic interaction between ZENAPAX and mycophenolic acid, the active metabolite of mycophenolate mofetil, was observed.
However, in a large clinical study in cardiac transplant recipients (n=434), the use of ZENAPAX as part of an immunosuppression regimen including cyclosporine, mycophenolate mofetil, and corticosteroids was associated with an increase in mortality, particularly in patients receiving concomitant anti-lymphocyte antibody therapy and in patients who developed severe infections (see WARNINGS and ADVERSE REACTIONS: Incidence of Infectious Episodes).
ZENAPAX is contraindicated in patients with known hypersensitivity to daclizumab or to any components of this product.
See Boxed WARNING.
The use of ZENAPAX as part of an immunosuppressive regimen including cyclosporine, mycophenolate mofetil, and corticosteroids may be associated with an increase in mortality. In a randomized, double-blind, placebo-controlled trial of ZENAPAX for the prevention of allograft rejection in 434 cardiac transplant recipients receiving concomitant cyclosporine, mycophenolate mofetil, and corticosteroids, mortality at 6 and 12 months was increased in those patients receiving ZENAPAX compared to those receiving placebo (7% vs 5%, respectively at 6 months; 10% vs 6% respectively at 12 months). Some, but not all, of the increase in mortality appeared related to a higher incidence of severe infections. Concomitant use of anti-lymphocyte antibody therapy may also be a factor in some of the fatal infections.
ZENAPAX should be administered under qualified medical supervision. Patients should be informed of the potential benefits of therapy and the risks associated with administration of immunosuppressive therapy.
While the incidence of lymphoproliferative disorders and opportunistic infections in the limited clinical trial experience was no higher in patients treated with ZENAPAX compared with placebo-treated patients, patients on immunosuppressive therapy are at increased risk for developing lymphoproliferative disorders and opportunistic infections and should be monitored accordingly.
Severe, acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to ZENAPAX and following re-exposure. These reactions may include hypotension, bronchospasm, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions. If a severe hypersensitivity reaction occurs, therapy with ZENAPAX should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use. Patients previously administered ZENAPAX should only be re-exposed to a subsequent course of therapy with caution. The potential risks of such re-administration, specifically those associated with immunosuppression, are not known.